Over the past 15 years, a large number of studies have been devoted to the primary prostaglandins, especially PGE2 and PGF2 alpha, and various physiological and pathological roles have been ascribed to them. The recent discovery that the same tissues that synthesize primary prostaglandins also produce arachidonic acid metabolites such as TxA2 and PGI2 with opposing biological properties calls for reevaluation of earlier data. In this proposal, we intend to investigate the contribution of prostaglandins and other arachidonic acid derivatives, such as prostacyclin and thromboxane, to the regulation of systemic blood pressure, regional blood flow, and vascular tone. To define this contribution, we will study the interaction of locally generated arachidonic acid derivatives with vasoactive hormones during pregnancy. The following aspects will be considered: 1. Factors that influence the release of the different prostaglandins or thromboxane from the pregnant and non-pregnant uterus. We will study the effect on releasing mechanisms as affected by endogenous activation or inhibition of the renin-angiotensin, kallikrein-kinin, and autonomic nervous systems, using an angiotensin II antagonist, an inhibitor of converting enzymes and a kallikrein inhibitor (Trasylol), as well as alpha and beta blocking agents. 2. Definition of changes in the products of cyclo-oxygenase during the progression of pregnancy. "In vitro" studies of the effect of added hormones, cofactors, and inhibitors on the rate of prostaglandin and thromboxane synthesis by bovine and human placenta and blood vessel slices. 3. Study of alterations in prostaglandin degradation during progression of pregnancy. We will explore, in an intact animal, the capacity of the lung and uterus to remove prostaglandins from the circulation at various stages of pregnancy. These studies will also be performed "in vitro" in tissues from toxemic patients and baboons. 4. Examination of one or more cyclo-oxygenase products in terms of their possible contribution to toxemia of pregnancy. Blood and urinary levels of prostaglandins will be measured at various stages of pregnancy and correlated with the variations in plasma renin activity, blood pressure, and urine volume.